There is considerable interest in the analysis of epigenetic alterations in cancer, including oral cancer and pre-cancerous lesions. These processes affect or inactivate the functions of genes without altering their structure or sequence. One example is the methylation of the promoter region of some genes involved in cell cycle control. Knowledge of methylation patterns is very important for understanding the expression of genes in normal and pathological situations. This review provides an update on research into this issue in oral cancer and pre-cancerous lesions. A greater understanding of this epigenetic alteration could not only assist the diagnosis and prognosis of oral cancer but could also open up novel therapeutic approaches. The presence of methylation in specific tumour suppressor genes could modify their function and alter cell cycle control, so the patients could have an increased risk of developing cancer and also a higher degree of malignancy. The most frequently and extensively studied methylated genes in oral premalignant lesions are p16, MGMT, RARβ2, E-cadherin and DAP-kinase.